The proposed research will deal with ultrastructural and functional changes in blood vessels, especially the endothelium, in the local response to injury. The experiments will examine vascular injury in the microcirculation and arteries, with regard to normal structure, vascular leakage, factors influencing endothelial detachment and endothelial regeneration. Mechanisms and kinetics of endothelial proliferation in acute inflammation and in tumor angiogenesis will be investigated. These studies will be relevant to understanding pathogenesis of edema formation, thrombosis, arteriosclerosis, repair and tumor growth. Studies on the renal microcirculation will include experiments on normal and abnormal permeability of glomerulus, peritubular, and medullary vessels with the aim of elucidating the mechanism of proteinuria and interstitial renal edema and the role of the vasa recta in urinary concentration and dilution. Methods used are electron microscopy, histochemistry, autoradiography, cytochemistry, enzyme tracer techniques, immunofluorescence microscopy and in vitro perfusion methods in well-defined experimental models.